Project Abstract The objective of this research is to understand the development of substance use (SU) from adolescence to adulthood, as a mediator of the cycle of childhood maltreatment and adult intimate partner violence (IPV; perpetrating and being a victim). We also consider the potential for gene-environment interactions on this developmental pathway by creating polygenic risk scores (PRS) for SU. The interaction between co-occurring childhood maltreatment exposures and genetic risk for SU are not fully evaluated for SU development from adolescence to adulthood. Further, SU problems and history of childhood maltreatment are both linked to perpetrating and becoming victims of violence, particularly intimate partner violence (IPV) during adulthood. Thus, it is likely that the developmental trajectory of SU is a mediator between multiple co-occurring childhood maltreatment exposures and IPV perpetration or victimization. However, it is also possible that this association is influenced (e.g., moderated) by genetic predispositions for SU pathology. The present study has several practical implications. A key practical implication of this work could include efficient identification of individuals at higher and lower risk of SU and IPV based on their maltreatment exposure and genetic risk. For example, it is possible that certain combinations of specific maltreatment exposures, but not genetics, could be key risk factors for SU and IPV. If this is true, then interventions that target individuals? behavior (i.e. SU and aggression) could be implemented. Specifically, for sub-groups with combination of maltreatment exposure that make youth most vulnerable for SU. Interventions that improve parenting practices and family functioning during childhood to reduce maltreatment exposure would be more likely to effectively reduce SU and IPV. Moreover, SU development could also be targeted to break the cycle of violence between childhood maltreatment and IPV. The genetic findings from this research contribute to the field of genetic epidemiology by proving greater insight into the biology of a complex public health problem (i.e. SU) and improve the efficacy of SU treatments.